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Published in: Critical Care 1/2018

Open Access 01-12-2018 | Research

Functional outcomes in adults with tuberculous meningitis admitted to the ICU: a multicenter cohort study

Authors: Marie Cantier, Adeline Morisot, Emmanuel Guérot, Bruno Megarbane, Keyvan Razazi, Damien Contou, Eric Mariotte, Emmanuel Canet, Etienne De Montmollin, Vincent Dubée, Eric Boulet, Stéphane Gaudry, Guillaume Voiriot, Julien Mayaux, Frédéric Pène, Mathilde Neuville, Bruno Mourvillier, Stéphane Ruckly, Lila Bouadma, Michel Wolff, Jean-François Timsit, Romain Sonneville, ENCEPHALITICA study group

Published in: Critical Care | Issue 1/2018

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Abstract

Background

Tuberculous meningitis (TBM) is a devastating infection in tuberculosis endemic areas with limited access to intensive care. Functional outcomes of severe adult TBM patients admitted to the ICU in nonendemic areas are not known.

Methods

We conducted a retrospective multicenter cohort study (2004–2016) of consecutive TBM patients admitted to 12 ICUs in the Paris area, France. Clinical, biological, and brain magnetic resonance imaging (MRI) findings at admission associated with a poor functional outcome (i.e., a score of 3–6 on the modified Rankin scale (mRS) at 90 days) were identified by logistic regression. Factors associated with 1-year mortality were investigated by Cox proportional hazards modeling.

Results

We studied 90 patients, of whom 61 (68%) had a score on the Glasgow Coma Scale ≤ 10 at presentation and 63 (70%) required invasive mechanical ventilation. Brain MRI revealed infarction and hydrocephalus in 38/75 (51%) and 25/75 (33%) cases, respectively. A poor functional outcome was observed in 55 (61%) patients and was independently associated with older age (adjusted odds ratio (aOR) 1.03, 95% CI 1.0–1.07), cerebrospinal fluid protein level ≥ 2 g/L (aOR 5.31, 95% CI 1.67–16.85), and hydrocephalus on brain MRI (aOR 17.2, 95% CI 2.57–115.14). By contrast, adjunctive steroids were protective (aOR 0.13, 95% CI 0.03–0.56). The multivariable adjusted hazard ratio of adjunctive steroids for 1-year mortality (47%, 95% CI 37%–59%) was 0.23 (95% CI 0.11–0.44). Among survivors at 1 year, functional independence (mRS of 0–2) was observed in 27/37 (73%, 95% CI 59%–87%) cases.

Conclusions

A poor functional outcome in adult TBM patients admitted to the ICU in a nonendemic area is observed in 60% of cases and is independently associated with elevated cerebrospinal fluid protein level and hydrocephalus. Our data also suggest a protective effect of adjunctive steroids, with reduced disability and mortality, irrespective of immune status and severity of disease at presentation. One-year follow-up revealed functional independence in most survivors.
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Literature
1.
go back to reference Mailles A, Stahl JP, Steering C, et al. Infectious encephalitis in France in 2007: a national prospective study. Clin Infect Dis. 2009;49:1838–47.CrossRefPubMed Mailles A, Stahl JP, Steering C, et al. Infectious encephalitis in France in 2007: a national prospective study. Clin Infect Dis. 2009;49:1838–47.CrossRefPubMed
2.
go back to reference Granerod J, Ambrose HE, Davies NW, et al. Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. Lancet Infect Dis. 2010;10:835–44.CrossRefPubMed Granerod J, Ambrose HE, Davies NW, et al. Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. Lancet Infect Dis. 2010;10:835–44.CrossRefPubMed
3.
go back to reference Verdon R, Chevret S, Laissy JP, et al. Tuberculous meningitis in adults: review of 48 cases. Clin Infect Dis. 1996;22:982–8.CrossRefPubMed Verdon R, Chevret S, Laissy JP, et al. Tuberculous meningitis in adults: review of 48 cases. Clin Infect Dis. 1996;22:982–8.CrossRefPubMed
4.
go back to reference Sonneville R, Gault N, de Montmollin E, et al. Clinical spectrum and outcomes of patients with encephalitis requiring intensive care. Eur J Neurol. 2015;22:6–16. e11CrossRefPubMed Sonneville R, Gault N, de Montmollin E, et al. Clinical spectrum and outcomes of patients with encephalitis requiring intensive care. Eur J Neurol. 2015;22:6–16. e11CrossRefPubMed
5.
go back to reference Wilkinson RJ, Rohlwink U, Misra UK, et al. Tuberculous meningitis. Nat Rev Neurol. 2017;13:581–98.CrossRefPubMed Wilkinson RJ, Rohlwink U, Misra UK, et al. Tuberculous meningitis. Nat Rev Neurol. 2017;13:581–98.CrossRefPubMed
6.
go back to reference Thwaites G, Fisher M, Hemingway C, et al. British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children. J Infect. 2009;59:167–87.CrossRefPubMed Thwaites G, Fisher M, Hemingway C, et al. British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children. J Infect. 2009;59:167–87.CrossRefPubMed
7.
go back to reference Mai NT, Thwaites GE. Recent advances in the diagnosis and management of tuberculous meningitis. Curr Opin Infect Dis. 2017;30:123–8.PubMed Mai NT, Thwaites GE. Recent advances in the diagnosis and management of tuberculous meningitis. Curr Opin Infect Dis. 2017;30:123–8.PubMed
8.
go back to reference Marais S, Thwaites G, Schoeman JF, et al. Tuberculous meningitis: a uniform case definition for use in clinical research. Lancet Infect Dis. 2010;10:803–12.CrossRefPubMed Marais S, Thwaites G, Schoeman JF, et al. Tuberculous meningitis: a uniform case definition for use in clinical research. Lancet Infect Dis. 2010;10:803–12.CrossRefPubMed
9.
go back to reference Erdem H, Ozturk-Engin D, Tireli H, et al. Hamsi scoring in the prediction of unfavorable outcomes from tuberculous meningitis: results of Haydarpasa-II study. J Neurol. 2015;262:890–8.CrossRefPubMed Erdem H, Ozturk-Engin D, Tireli H, et al. Hamsi scoring in the prediction of unfavorable outcomes from tuberculous meningitis: results of Haydarpasa-II study. J Neurol. 2015;262:890–8.CrossRefPubMed
10.
go back to reference Heemskerk AD, Bang ND, Mai NT, et al. Intensified antituberculosis therapy in adults with tuberculous meningitis. N Engl J Med. 2016;374:124–34.CrossRefPubMed Heemskerk AD, Bang ND, Mai NT, et al. Intensified antituberculosis therapy in adults with tuberculous meningitis. N Engl J Med. 2016;374:124–34.CrossRefPubMed
11.
go back to reference Thao LTP, Heemskerk AD, Geskus RB, et al. Prognostic models for 9-month mortality in tuberculous meningitis. Clin Infect Dis. 2018;66:523–32.CrossRefPubMed Thao LTP, Heemskerk AD, Geskus RB, et al. Prognostic models for 9-month mortality in tuberculous meningitis. Clin Infect Dis. 2018;66:523–32.CrossRefPubMed
12.
go back to reference Heemskerk AD, Nguyen MTH, Dang HTM, et al. Clinical outcomes of patients with drug-resistant tuberculous meningitis treated with an intensified antituberculosis regimen. Clin Infect Dis. 2017;65:20–8.CrossRefPubMedPubMedCentral Heemskerk AD, Nguyen MTH, Dang HTM, et al. Clinical outcomes of patients with drug-resistant tuberculous meningitis treated with an intensified antituberculosis regimen. Clin Infect Dis. 2017;65:20–8.CrossRefPubMedPubMedCentral
13.
go back to reference Thwaites GE, Nguyen DB, Nguyen HD, et al. Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults. N Engl J Med. 2004;351:1741–51.CrossRefPubMed Thwaites GE, Nguyen DB, Nguyen HD, et al. Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults. N Engl J Med. 2004;351:1741–51.CrossRefPubMed
14.
go back to reference Prasad K, Singh MB, Ryan H. Corticosteroids for managing tuberculous meningitis. Cochrane Database Syst Rev. 2016;4:CD002244.PubMed Prasad K, Singh MB, Ryan H. Corticosteroids for managing tuberculous meningitis. Cochrane Database Syst Rev. 2016;4:CD002244.PubMed
15.
go back to reference Keim LW, Schuldt S, Bedell GN. Tuberculosis in the intensive care unit. Heart Lung. 1977;6:624–34.PubMed Keim LW, Schuldt S, Bedell GN. Tuberculosis in the intensive care unit. Heart Lung. 1977;6:624–34.PubMed
16.
go back to reference Madani N, Dendane T, Zekraoui A, et al. Effects of corticosteroids on adults with tuberculous meningitis admitted to intensive care unit: a propensity score analysis. Rev Med Interne. 2009;30:12–9.CrossRefPubMed Madani N, Dendane T, Zekraoui A, et al. Effects of corticosteroids on adults with tuberculous meningitis admitted to intensive care unit: a propensity score analysis. Rev Med Interne. 2009;30:12–9.CrossRefPubMed
17.
go back to reference Misra UK, Kalita J, Betai S, et al. Outcome of tuberculous meningitis patients requiring mechanical ventilation. J Crit Care. 2015;30:1365–9.CrossRefPubMed Misra UK, Kalita J, Betai S, et al. Outcome of tuberculous meningitis patients requiring mechanical ventilation. J Crit Care. 2015;30:1365–9.CrossRefPubMed
18.
go back to reference Marais BJ, Heemskerk AD, Marais SS, et al. Standardized methods for enhanced quality and comparability of tuberculous meningitis studies. Clin Infect Dis. 2017;64:501–9.CrossRefPubMed Marais BJ, Heemskerk AD, Marais SS, et al. Standardized methods for enhanced quality and comparability of tuberculous meningitis studies. Clin Infect Dis. 2017;64:501–9.CrossRefPubMed
19.
go back to reference Knaus WA, Zimmerman JE, Wagner DP, et al. APACHE—Acute Physiology and Chronic Health Evaluation: a physiologically based classification system. Crit Care Med. 1981;9:591–7.CrossRefPubMed Knaus WA, Zimmerman JE, Wagner DP, et al. APACHE—Acute Physiology and Chronic Health Evaluation: a physiologically based classification system. Crit Care Med. 1981;9:591–7.CrossRefPubMed
20.
go back to reference Thwaites GE, Macmullen-Price J, Tran TH, et al. Serial MRI to determine the effect of dexamethasone on the cerebral pathology of tuberculous meningitis: an observational study. Lancet Neurol. 2007;6:230–6.CrossRefPubMedPubMedCentral Thwaites GE, Macmullen-Price J, Tran TH, et al. Serial MRI to determine the effect of dexamethasone on the cerebral pathology of tuberculous meningitis: an observational study. Lancet Neurol. 2007;6:230–6.CrossRefPubMedPubMedCentral
21.
go back to reference Graham SM, Donald PR. Death and disability: the outcomes of tuberculous meningitis. Lancet Infect Dis. 2014;14:902–4.CrossRefPubMed Graham SM, Donald PR. Death and disability: the outcomes of tuberculous meningitis. Lancet Infect Dis. 2014;14:902–4.CrossRefPubMed
22.
go back to reference Kalita J, Misra UK, Ranjan P. Predictors of long-term neurological sequelae of tuberculous meningitis: a multivariate analysis. Eur J Neurol. 2007;14:33–7.CrossRefPubMed Kalita J, Misra UK, Ranjan P. Predictors of long-term neurological sequelae of tuberculous meningitis: a multivariate analysis. Eur J Neurol. 2007;14:33–7.CrossRefPubMed
23.
go back to reference George EL, Iype T, Cherian A, et al. Predictors of mortality in patients with meningeal tuberculosis. Neurol India. 2012;60:18–22.CrossRefPubMed George EL, Iype T, Cherian A, et al. Predictors of mortality in patients with meningeal tuberculosis. Neurol India. 2012;60:18–22.CrossRefPubMed
26.
go back to reference Raut T, Garg RK, Jain A, et al. Hydrocephalus in tuberculous meningitis: incidence, its predictive factors and impact on the prognosis. J Inf Secur. 2013;66:330–7. Raut T, Garg RK, Jain A, et al. Hydrocephalus in tuberculous meningitis: incidence, its predictive factors and impact on the prognosis. J Inf Secur. 2013;66:330–7.
27.
go back to reference Chou CH, Lin GM, Ku CH, et al. Comparison of the APACHE II, GCS and MRC scores in predicting outcomes in patients with tuberculous meningitis. Int J Tuberc Lung Dis. 2010;14:86–92.PubMed Chou CH, Lin GM, Ku CH, et al. Comparison of the APACHE II, GCS and MRC scores in predicting outcomes in patients with tuberculous meningitis. Int J Tuberc Lung Dis. 2010;14:86–92.PubMed
28.
go back to reference Tandon V, Mahapatra AK. Management of post-tubercular hydrocephalus. Childs Nerv Syst. 2011;27:1699–707.CrossRefPubMed Tandon V, Mahapatra AK. Management of post-tubercular hydrocephalus. Childs Nerv Syst. 2011;27:1699–707.CrossRefPubMed
29.
go back to reference Schoeman JF, Elshof JW, Laubscher JA, et al. The effect of adjuvant steroid treatment on serial cerebrospinal fluid changes in tuberculous meningitis. Ann Trop Paediatr. 2001;21:299–305.CrossRefPubMed Schoeman JF, Elshof JW, Laubscher JA, et al. The effect of adjuvant steroid treatment on serial cerebrospinal fluid changes in tuberculous meningitis. Ann Trop Paediatr. 2001;21:299–305.CrossRefPubMed
30.
go back to reference van der Flier M, Hoppenreijs S, van Rensburg AJ, et al. Vascular endothelial growth factor and blood-brain barrier disruption in tuberculous meningitis. Pediatr Infect Dis J. 2004;23:608–13.CrossRefPubMed van der Flier M, Hoppenreijs S, van Rensburg AJ, et al. Vascular endothelial growth factor and blood-brain barrier disruption in tuberculous meningitis. Pediatr Infect Dis J. 2004;23:608–13.CrossRefPubMed
Metadata
Title
Functional outcomes in adults with tuberculous meningitis admitted to the ICU: a multicenter cohort study
Authors
Marie Cantier
Adeline Morisot
Emmanuel Guérot
Bruno Megarbane
Keyvan Razazi
Damien Contou
Eric Mariotte
Emmanuel Canet
Etienne De Montmollin
Vincent Dubée
Eric Boulet
Stéphane Gaudry
Guillaume Voiriot
Julien Mayaux
Frédéric Pène
Mathilde Neuville
Bruno Mourvillier
Stéphane Ruckly
Lila Bouadma
Michel Wolff
Jean-François Timsit
Romain Sonneville
ENCEPHALITICA study group
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2018
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-018-2140-8

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